Medical Care as Flea Market Bargaining? An International Interdisciplinary Study of Varieties of Shared Decision Making in Physician-Patient Interactions.

Phenomenon: Shared decision making (SDM) is a core ideal in the interaction between healthcare providers and patients, but the implementation of the SDM ideal in clinical routines has been a relatively slow process. Approach: In a sociological study, 71 interactions between physicians and simulated patients enacting chronic heart failure were video-recorded in China, Germany, the Netherlands, and Turkey as part of a quasi-experimental research design. Participating physicians varied in specialty and level of experience. The secondary analysis presented in this article used content analysis to study core components of SDM in all of the 71 interactions and a grounded theory approach to observe how physicians responded actively to patients even though they did not actively employ the SDM ideal. Findings: Full realization of the SDM ideal remains an exception, but various aspects of SDM in physician-patient interaction were observed in all four locations. Analyses of longer interactions show dynamic processes of interaction that sometimes surprised both patient and physician. We observed varieties of SDM that differ from the SDM ideal but arguably achieve what the SDM ideal is intended to achieve. Our analysis suggests a need to revisit the SDM ideal-to consider whether varieties of SDM may be acceptable, even valuable, in their own right. Insights: The gap between the SDM ideal and SDM as implemented in clinical practice may in part be explained by the tendency of medicine to define and teach SDM through a narrow lens of checklist evaluations. The authors support the argument that SDM defies a checklist approach. SDM is not uniform, but nuanced, dependent on circumstances and setting. As SDM is co-produced by patients and physicians in a dynamic process of interaction, medical researchers should consider and medical learners should be exposed to varieties of SDM-related practice rather than a single idealized model. Observing and discussing worked examples contributes to the physician's development of realistic expectations and personal professional growth.

Electrocardiogram-based deep learning improves outcome prediction following cardiac resynchronization therapy.

AIMS: This study aims to identify and visualize electrocardiogram (ECG) features using an explainable deep learning-based algorithm to predict cardiac resynchronization therapy (CRT) outcome. Its performance is compared with current guideline ECG criteria and QRSAREA. METHODS AND RESULTS: A deep learning algorithm, trained on 1.1 million ECGs from 251 473 patients, was used to compress the median beat ECG, thereby summarizing most ECG features into only 21 explainable factors (FactorECG). Pre-implantation ECGs of 1306 CRT patients from three academic centres were converted into their respective FactorECG. FactorECG predicted the combined clinical endpoint of death, left ventricular assist device, or heart transplantation [c-statistic 0.69, 95% confidence interval (CI) 0.66-0.72], significantly outperforming QRSAREA and guideline ECG criteria [c-statistic 0.61 (95% CI 0.58-0.64) and 0.57 (95% CI 0.54-0.60), P < 0.001 for both]. The addition of 13 clinical variables was of limited added value for the FactorECG model when compared with QRSAREA (Δ c-statistic 0.03 vs. 0.10). FactorECG identified inferolateral T-wave inversion, smaller right precordial S- and T-wave amplitude, ventricular rate, and increased PR interval and P-wave duration to be important predictors for poor outcome. An online visualization tool was created to provide interactive visualizations (https://crt.ecgx.ai). CONCLUSION: Requiring only a standard 12-lead ECG, FactorECG held superior discriminative ability for the prediction of clinical outcome when compared with guideline criteria and QRSAREA, without requiring additional clinical variables. End-to-end automated visualization of ECG features allows for an explainable algorithm, which may facilitate rapid uptake of this personalized decision-making tool in CRT.

Assessment of ICD eligibility in non-ischaemic cardiomyopathy patients: a position statement by the Task Force of the Dutch Society of Cardiology.

International guidelines recommend implantation of an implantable cardioverter-defibrillator (ICD) in non-ischaemic cardiomyopathy (NICM) patients with a left ventricular ejection fraction (LVEF) below 35% despite optimal medical therapy and a life expectancy of more than 1 year with good functional status. We propose refinement of these recommendations in patients with NICM, with careful consideration of additional risk parameters for both arrhythmic and non-arrhythmic death. These additional parameters include late gadolinium enhancement on cardiac magnetic resonance imaging and genetic testing for high-risk genetic variants to further assess arrhythmic risk, and age, comorbidities and sex for assessment of non-arrhythmic mortality risk. Moreover, several risk modifiers should be taken into account, such as concomitant arrhythmias that may affect LVEF (atrial fibrillation, premature ventricular beats) and resynchronisation therapy. Even though currently no valid cut-off values have been established, the proposed approach provides a more careful consideration of risks that may result in withholding ICD implantation in patients with low arrhythmic risk and substantial non-arrhythmic mortality risk.

Comparison of the relation of the ESC 2021 and ESC 2013 definitions of left bundle branch block with clinical and echocardiographic outcome in cardiac resynchronization therapy.

INTRODUCTION: We aimed to investigate the impact of the 2021 European Society of Cardiology (ESC) guideline changes in left bundle branch block (LBBB) definition on cardiac resynchronization therapy (CRT) patient selection and outcomes. METHODS: The MUG (Maastricht, Utrecht, Groningen) registry, consisting of consecutive patients implanted with a CRT device between 2001 and 2015 was studied. For this study, patients with baseline sinus rhythm and QRS duration ≥ 130ms were eligible. Patients were classified according to ESC 2013 and 2021 guideline LBBB definitions and QRS duration. Endpoints were heart transplantation, LVAD implantation or mortality (HTx/LVAD/mortality) and echocardiographic response (LVESV reduction ≥15%). RESULTS: The analyses included 1.202, typical CRT patients. The ESC 2021 definition resulted in considerably less LBBB diagnoses compared to the 2013 definition (31.6% vs. 80.9%, respectively). Applying the 2013 definition resulted in significant separation of the Kaplan-Meier curves of HTx/LVAD/mortality (p < .0001). A significantly higher echocardiographic response rate was found in the LBBB compared to the non-LBBB group using the 2013 definition. These differences in HTx/LVAD/mortality and echocardiographic response were not found when applying the 2021 definition. CONCLUSION: The ESC 2021 LBBB definition leads to a considerably lower percentage of patients with baseline LBBB then the ESC 2013 definition. This does not lead to better differentiation of CRT responders, nor does this lead to a stronger association with clinical outcomes after CRT. In fact, stratification according to the 2021 definition is not associated with a difference in clinical or echocardiographic outcome, implying that the guideline changes may negatively influence CRT implantation practice with a weakened recommendation in patients that will benefit from CRT.

Association of vectorcardiographic T-wave area with clinical and echocardiographic outcomes in cardiac resynchronization therapy.

AIMS: Data on repolarization parameters in cardiac resynchronization therapy (CRT) are scarce. We investigated the association of baseline T-wave area, with both clinical and echocardiographic outcomes of CRT in a large, multi-centre cohort of CRT recipients. Also, we evaluated the association between the baseline T-wave area and QRS area. METHODS AND RESULTS: In this retrospective study, 1355 consecutive CRT recipients were evaluated. Pre-implantation T-wave and QRS area were calculated from vectorcardiograms. Echocardiographic response was defined as a reduction of ≥15% in left ventricular end-systolic volume between 3 and 12 months after implantation. The clinical outcome was a combination of all-cause mortality, heart transplantation, and left ventricular assist device implantation. Left ventricular end-systolic volume reduction was largest in patients with QRS area ≥ 109 µVs and T-wave area ≥ 66 µVs compared with QRS area ≥ 109 µVs and T-wave area < 66 µVs (P = 0.004), QRS area < 109 µVs and T-wave area ≥ 66 µVs (P < 0.001) and QRS area < 109 µVs and T-wave area < 66 µVs (P < 0.001). Event-free survival rate was higher in the subgroup of patients with QRS area ≥ 109 µVs and T-wave area ≥ 66 µVs (n = 616, P < 0.001) and QRS area ≥ 109 µVs and T-wave area < 66 µVs (n = 100, P < 0.001) than the other subgroups. In the multivariate analysis, T-wave area remained associated with echocardiographic response (P = 0.008), but not with the clinical outcome (P = 0.143), when QRS area was included in the model. CONCLUSION: Baseline T-wave area has a significant association with both clinical and echocardiographic outcomes after CRT. The association of T-wave area with echocardiographic response is independent from QRS area; the association with clinical outcome, however, is not.

Hearts in their hands-Physicians' gestures embodying shared professional knowledge around the world.

The biomedical approach to medical knowledge is widely accepted around the world. This article considers whether the incorporated aspects of physician-patient interaction have become similarly common across the globe by comparing the gestures that physicians use in their interactions with patients. Up to this point, there has been little research on physicians' use of gestures in health-care settings. We explore how-in four university hospitals in Turkey, the People's Republic of China, The Netherlands and Germany-physicians use gesture in their discussions with simulated patients about the condition of heart failure. Our analysis confirms the importance of gestures for organising both the personal interaction and the knowledge transfer between physician and patient. From the perspective of global comparison, it is notable that physicians in all four hospitals used similar gestures. This demonstrates the globality of biomedical knowledge in an embodied mode. Physicians used gestures for a range of purposes, including to convey the idea of an 'anatomical map' and for constructing visual models of (patho-)physiological processes. Since biomedical language is rife with metaphor, it was not surprising that we also identified an accompanying metaphorical gesture which has a similar form in the various locations that were part of the study.

NL-EVDR: Netherlands-ExtraVascular Device Registry.

Cardiac implantable electronic device (CIED) therapy is an essential element in treating cardiac arrhythmias. Despite their benefits, conventional transvenous CIEDs are associated with a significant risk of mainly pocket- and lead-related complications. To overcome these complications, extravascular devices (EVDs), such as the subcutaneous implantable cardioverter-defibrillator and intracardiac leadless pacemaker, have been developed. In the near future, several other innovative EVDs will become available. However, it is difficult to evaluate EVDs in large studies because of high costs, lack of long-term follow-up, imprecise data or selected patient populations. To improve evaluation of these technologies, real-world, large-scale, long-term data are of utmost importance. A Dutch registry-based study seems to be a unique possibility for this goal due to early involvement of Dutch hospitals in novel CIEDs and an existing quality control infrastructure, the Netherlands Heart Registration (NHR). Therefore, we will soon start the Netherlands-ExtraVascular Device Registry (NL-EVDR), a Dutch nationwide registry with long-term follow-up of EVDs. The NL-EVDR will be incorporated in NHR's device registry. Additional EVD-specific variables will be collected both retrospectively and prospectively. Hence, combining Dutch EVD data will provide highly relevant information on safety and efficacy. As a first step, a pilot project has started in selected centres in October 2022 to optimise data collection.

The erythropoietin receptor expressed in skeletal muscle is essential for mitochondrial biogenesis and physiological exercise.

Erythropoietin (EPO) is a haematopoietic hormone that regulates erythropoiesis, but the EPO-receptor (EpoR) is also expressed in non-haematopoietic tissues. Stimulation of the EpoR in cardiac and skeletal muscle provides protection from various forms of pathological stress, but its relevance for normal muscle physiology remains unclear. We aimed to determine the contribution of the tissue-specific EpoR to exercise-induced remodelling of cardiac and skeletal muscle. Baseline phenotyping was performed on left ventricle and m. gastrocnemius of mice that only express the EpoR in haematopoietic tissues (EpoR-tKO). Subsequently, mice were caged in the presence or absence of a running wheel for 4 weeks and exercise performance, cardiac function and histological and molecular markers for physiological adaptation were assessed. While gross morphology of both muscles was normal in EpoR-tKO mice, mitochondrial content in skeletal muscle was decreased by 50%, associated with similar reductions in mitochondrial biogenesis, while mitophagy was unaltered. When subjected to exercise, EpoR-tKO mice ran slower and covered less distance than wild-type (WT) mice (5.5 ± 0.6 vs. 8.0 ± 0.4 km/day, p < 0.01). The impaired exercise performance was paralleled by reductions in myocyte growth and angiogenesis in both muscle types. Our findings indicate that the endogenous EPO-EpoR system controls mitochondrial biogenesis in skeletal muscle. The reductions in mitochondrial content were associated with reduced exercise capacity in response to voluntary exercise, supporting a critical role for the extra-haematopoietic EpoR in exercise performance.

Reduction in the QRS area after cardiac resynchronization therapy is associated with survival and echocardiographic response.

INTRODUCTION: Recent studies have shown that the baseline QRS area is associated with the clinical response after cardiac resynchronization therapy (CRT). In this study, we investigated the association of QRS area reduction (∆QRS area) after CRT with the outcome. We hypothesize that a larger ∆QRS area is associated with a better survival and echocardiographic response. METHODS AND RESULTS: Electrocardiograms (ECG) obtained before and 2-12 months after CRT from 1299 patients in a multi-center CRT-registry were analyzed. The QRS area was calculated from vectorcardiograms that were synthesized from 12-lead ECGs. The primary endpoint was a combination of all-cause mortality, heart transplantation, and left ventricular (LV) assist device implantation. The secondary endpoint was the echocardiographic response, defined as LV end-systolic volume reduction ≥ of 15%. Patients with ∆QRS area above the optimal cut-off value (62 µVs) had a lower risk of reaching the primary endpoint (hazard ratio: 0.43; confidence interval [CI] 0.33-0.56, p < .001), and a higher chance of echocardiographic response (odds ratio [OR] 3.3;CI 2.4-4.6, p < .0001). In multivariable analysis, ∆QRS area was independently associated with both endpoints. In patients with baseline QRS area ≥109 µVs, survival, and echocardiographic response were better when the ∆QRS area was ≥62 µVs (p < .0001). Logistic regression showed that in patients with baseline QRS area ≥109 µVs, ∆QRS area was the only significant predictor of survival (OR: 0.981; CI: 0.967-0.994, p = .006). CONCLUSION: ∆QRS area is an independent determinant of CRT response, especially in patients with a large baseline QRS area. Failure to achieve a large QRS area reduction with CRT is associated with a poor clinical outcome.

Segment length in cine (SLICE) strain analysis: a practical approach to estimate potential benefit from cardiac resynchronization therapy.

BACKGROUND: Segment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response. METHODS AND RESULTS: Fifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRSsep), systolic stretch index (SSIsep-lat), and internal stretch factor (ISFsep-lat) all correlated significantly with LVESV change (R - 0.56; R - 0.53; and R - 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESSsep) showed strongest correlation with LVESV change (R - 0.63). Multivariable analysis showed ESSsep to be independently related to LVESV change together with age and QRSAREA. CONCLUSION: The practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESSsep) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted.

Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death.

AIMS: This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation. METHODS AND RESULTS: We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality. CONCLUSION: Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.

Temporal patterns and short-term progression of paroxysmal atrial fibrillation: data from RACE V.

AIMS: Atrial fibrillation (AF) often starts as a paroxysmal self-terminating arrhythmia. Limited information is available on AF patterns and episode duration of paroxysmal AF. In paroxysmal AF patients, we longitudinally studied the temporal AF patterns, the association with clinical characteristics, and prevalence of AF progression. METHODS AND RESULTS: In this interim analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) registry, 202 patients with paroxysmal AF were followed with continuous rhythm monitoring (implantable loop recorder or pacemaker) for 6 months. Mean age was 64 ± 9 years, 42% were women. Atrial fibrillation history was 2.1 (0.5-4.4) years, CHA2DS2-VASc 1.9 ± 1.3, 101 (50%) had hypertension, 69 (34%) heart failure. One-third had no AF during follow-up. Patients with long episodes (>12 hours) were often men with more comorbidities (heart failure, coronary artery disease, higher left ventricular mass). Patients with higher AF burden (>2.5%) were older with more comorbidities (worse renal function, higher calcium score, thicker intima media thickness). In 179 (89%) patients, 1-year rhythm follow-up was available. On a quarterly basis, average daily AF burden increased from 3.2% to 3.8%, 5.2%, and 6.1%. Compared to the first 6 months, 111 (62%) patients remained stable during the second 6 months, 39 (22%) showed progression to longer AF episodes, 8 (3%) developed persistent AF, and 29 (16%) patients showed AF regression. CONCLUSIONS: In paroxysmal AF, temporal patterns differ suggesting that paroxysmal AF is not one entity. Atrial fibrillation burden is low and determined by number of comorbidities. Atrial fibrillation progression occurred in a substantial number. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier NCT02726698.

Fully automated QRS area measurement for predicting response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and conduction abnormalities. However, a significant number of patients do not respond to CRT. Currently employed criteria for selection of patients for this therapy (QRS duration and morphology) have several shortcomings. QRS area was recently shown to provide superior association with CRT response. However, its assessment was not fully automated and required the presence of an expert. OBJECTIVE: Our objective was to develop a fully automated method for the assessment of vector-cardiographic (VCG) QRS area from electrocardiographic (ECG) signals. METHODS: Pre-implantation ECG recordings (N = 864, 695 left-bundle-branch block, 589 men) in PDF files were converted to allow signal processing. QRS complexes were found and clustered into morphological groups. Signals were converted from 12­lead ECG to 3­lead VCG and an average QRS complex was built. QRS area was computed from individual areas in the X, Y and Z leads. Practical usability was evaluated using Kaplan-Meier plots and 5-year follow-up data. RESULTS: The automatically calculated QRS area values were 123 ±â€¯48 µV.s (mean values and SD), while the manually determined QRS area values were 116 ±â€¯51 ms; the correlation coefficient between the two was r = 0.97. The automated and manual methods showed the same ability to stratify the population (hazard ratios 2.09 vs 2.03, respectively). CONCLUSION: The presented approach allows the fully automatic and objective assessment of QRS area values. SIGNIFICANCE: Until this study, assessing QRS area values required an expert, which means both additional costs and a risk of subjectivity. The presented approach eliminates these disadvantages and is publicly available as part of free signal-processing software.

Heart failure with preserved ejection fraction, atrial fibrillation, and the role of senile amyloidosis.

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are very common conditions, particularly in the elderly. However, the mechanisms underlying the two disorders, including their intricate interaction have not been fully resolved. Here, our aim is to review the evidence on the role of the two types of senile amyloidosis in this connection. Two types of senile amyloidosis can be identified: wild-type transthyretin (TTR)-derived amyloidosis (ATTRwt) and isolated atrial amyloidosis (IAA). ATTRwt is an underlying condition that is being increasingly recognized in patients with HFpEF and often accompanied by AF. IAA is an established cause of AF, adding to the mechanism problem. New diagnostic and therapeutic possibilities have emerged that may facilitate clinical management of (senile) amyloidosis, which in turn may have implications for the management of HFpEF and AF.

Response to Cardiac Resynchronization Therapy Across Chronic Kidney Disease Stages.

INTRODUCTION: Limited data are available concerning the effect of severe chronic kidney disease (CKD) on the response to cardiac resynchronization therapy (CRT) because these patients are commonly excluded from trials. Therefore, we aimed to assess the effect of CRT on renal function, reverse remodeling and outcome across all stages of CKD in a large patient population of recipients of CRT. METHODS: We retrospectively evaluated 798 consecutive patients with heart failure who were undergoing CRT implantation between October 2008 and September 2016. Renal function data were available at baseline and at 6 months following CRT. Remodeling based on left ventricular end diastolic volume/left ventricular ejection fraction (LVESV/LVEF) and clinical outcome was assessed using a combined endpoint of all-cause mortality and hospitalization because of heart failure. RESULTS: Median baseline estimated glomerular filtration rate was 62.8 (43.6-77.8) mL/min/1.73 m2. Of the patients, 33.6% were in CKD stage 3, 11.0% in stage 4 and 1.1% in stage 5. LVEF and LVESV improved across all CKD stages; however, patients with CKD stages 1 and 2 exhibited a greater degree of improvement in LVEF (median 15% vs 10%, P < 0.001) and LVESV (median -37.2% vs -29.9%, P < 0.001) compared to patients with CKD stages 3-5. Despite a greater degree of reverse remodeling in CKD stages 1 and 2, the most accurate cut-off of remodeling predicting good clinical outcome was lower for patients with CKD stage 3-5, respectively: 5.5% vs 9.5% (LVEF) and -6.67% vs -12.41% (LVESV). CONCLUSIONS: CRT results in reverse remodeling across all stages of CKD, although to a lesser extent in patients with renal dysfunction (CKD stage 3-5). However, patients with CKD derive benefit on outcome at a lesser degree of remodeling.

Six-year follow-up of the initial Dutch subcutaneous implantable cardioverter-defibrillator cohort: Long-term complications, replacements, and battery longevity.

INTRODUCTION: Experience with the subcutaneous implantable cardioverter-defibrillator (S-ICD) is expanding rapidly. However, data on long-term performance or complications related to elective generator replacement are lacking. METHODS: Follow-up (FU) data of all patients implanted between December 2008 and April 2011 were collected. Complications were defined as those requiring surgical intervention. Kaplan-Meier estimates for complication and shock rates, with corresponding 95% confidence intervals (CI), were calculated. RESULTS: One hundred and eighteen patients were included. Median FU was 6.1 years (IQR 5.6-6.5 years). Short-term complication rate (0-30 days) was 3% (CI 0-6%). Long-term complication rate at 6 years was 19% (CI 12-26%), corresponding with an annual complication rate of 3%. One patient in this cohort developed a need for a transvenous ICD (TV-ICD) in order to provide pacing for bradycardia (1%). Six patients were implanted with a TV-ICD after experiencing an S-ICD complication for which extraction was necessary. In total, 10 S-ICDs were extracted; none resulted in a complication. Eight patients had a nonsystemic ICD-related infection and no lead failures were observed. The majority, 68 (58%) patients, received an elective generator replacement. Two patients had a complication related to generator replacement (3%). Battery longevity was 5.6 years (IQR 5.2-6.1). Appropriate and inappropriate shock rates of 6-year estimates were 17% (CI 9-25%) and 21% (CI 15-27%), respectively. CONCLUSIONS: This cohort represents the longest follow-up to date and shows a low annual complication rate without lead failures or systemic infections. Battery longevity of the first S-ICD generation results in relative early generator replacement procedures.

Tailoring device settings in cardiac resynchronization therapy using electrograms from pacing electrodes.

Aims: Left ventricular (LV) fusion pacing appears to be at least as beneficial as biventricular pacing in cardiac resynchronization therapy (CRT). Optimal LV fusion pacing critically requires adjusting the atrioventricular (AV)-delay to the delay between atrial pacing and intrinsic right ventricular (RV) activation (Ap-RV). We explored the use of electrogram (EGM)-based vectorloop (EGMV) derived from EGMs of implanted pacing leads to achieve optimal LV fusion pacing and to compare it with conventional approaches. Methods and results: During CRT-device implantation, 28 patients were prospectively studied. During atrial-LV pacing (Ap-LVp) at various AV-delays, LV dP/dtmax, 12-lead electrocardiogram (ECG), and unipolar EGMs were recorded. Electrocardiogram and electrogram were used to reconstruct a vectorcardiogram (VCG) and EGMV, respectively, from which the maximum QRS amplitude (QRSampl), was extracted. Ap-RV was determined: (i) conventionally as the longest AV-delay at which QRS morphology was visually unaltered during RV pacing at increasing AV-delays(Ap-RVvis; reference-method); (ii) 70% of delay between atrial pacing and RV sensing (Ap-RVaCRT); and (iii) the delay between atrial pacing and onset of QRS (Ap-QRSonset). In both the EGMV and VCG, the longest AV-delay showing an unaltered QRSampl as compared with Ap-LVp with a short AV-delay, corresponded to Ap-RVvis. In contrast, Ap-QRSonset and Ap-RVaCRT were larger. The Ap-LVp induced increase in LV dP/dtmax was larger at Ap-RVvis, Ap-RVEGMV, and Ap-RVVCG than at Ap-QRSonset (all P < 0.05) and Ap-RVaCRT (P = 0.02, P = 0.13, and P = 0.03, respectively). Conclusion: In this acute study, it is shown that the EGMV QRSampl can be used to determine optimal and individual CRT-device settings for LV fusion pacing, possibly improving long-term CRT response.

Refining success of cardiac resynchronization therapy using a simple score predicting the amount of reverse ventricular remodelling: results from the Markers and Response to CRT (MARC) study.

Aims: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in systolic heart failure patients with ventricular conduction delay. Variability of individual response to CRT warrants improved patient selection. The Markers and Response to CRT (MARC) study was designed to investigate markers related to response to CRT. Methods and results: We prospectively studied the ability of 11 clinical, 11 electrocardiographic, 4 echocardiographic, and 16 blood biomarkers to predict CRT response in 240 patients. Response was measured by the reduction of indexed left ventricular end-systolic volume (LVESVi) at 6 months follow-up. Biomarkers were related to LVESVi change using log-linear regression on continuous scale. Covariates that were significant univariately were included in a multivariable model. The final model was utilized to compose a response score. Age was 67 ± 10 years, 63% were male, 46% had ischaemic aetiology, LV ejection fraction was 26 ± 8%, LVESVi was 75 ± 31 mL/m2, and QRS was 178 ± 23 ms. At 6 months LVESVi was reduced to 58 ± 31 mL/m2 (relative reduction of 22 ± 24%), 130 patients (61%) showed ≥ 15% LVESVi reduction. In univariate analysis 17 parameters were significantly associated with LVESVi change. In the final model age, QRSAREA (using vectorcardiography) and two echocardiographic markers (interventricular mechanical delay and apical rocking) remained significantly associated with the amount of reverse ventricular remodelling. This CAVIAR (CRT-Age-Vectorcardiographic QRSAREA -Interventricular Mechanical delay-Apical Rocking) response score also predicted clinical outcome assessed by heart failure hospitalizations and all-cause mortality. Conclusions: The CAVIAR response score predicts the amount of reverse remodelling after CRT and may be used to improve patient selection. Clinical Trials: NCT01519908.

Hypercoagulability causes atrial fibrosis and promotes atrial fibrillation.

AIMS: Atrial fibrillation (AF) produces a hypercoagulable state. Stimulation of protease-activated receptors by coagulation factors provokes pro-fibrotic, pro-hypertrophic, and pro-inflammatory responses in a variety of tissues. We studied the effects of thrombin on atrial fibroblasts and tested the hypothesis that hypercoagulability contributes to the development of a substrate for AF. METHODS AND RESULTS: In isolated rat atrial fibroblasts, thrombin enhanced the phosphorylation of the pro-fibrotic signalling molecules Akt and Erk and increased the expression of transforming growth factor ß1 (2.7-fold) and the pro-inflammatory factor monocyte chemoattractant protein-1 (6.1-fold). Thrombin also increased the incorporation of 3H-proline, suggesting enhanced collagen synthesis by fibroblasts (2.5-fold). All effects could be attenuated by the thrombin inhibitor dabigatran. In transgenic mice with a pro-coagulant phenotype (TMpro/pro), the inducibility of AF episodes lasting >1 s was higher (7 out of 12 vs. 1 out of 10 in wild type) and duration of AF episodes was longer compared with wild type mice (maximum episode duration 42.8 ± 68.4 vs. 0.23 ± 0.39 s). In six goats with persistent AF treated with nadroparin, targeting Factor Xa-mediated thrombin generation, the complexity of the AF substrate was less pronounced than in control animals (LA maximal activation time differences 23.3 ± 3.1 ms in control vs. 15.7 ± 2.1 ms in nadroparin, P < 0.05). In the treated animals, AF-induced α-smooth muscle actin expression was lower and endomysial fibrosis was less pronounced. CONCLUSION: The hypercoagulable state during AF causes pro-fibrotic and pro-inflammatory responses in adult atrial fibroblasts. Hypercoagulability promotes the development of a substrate for AF in transgenic mice and in goats with persistent AF. In AF goats, nadroparin attenuates atrial fibrosis and the complexity of the AF substrate. Inhibition of coagulation may not only prevent strokes but also inhibit the development of a substrate for AF.